It is well known that the mast cells and basophils are the initial players in the pathogenesis of allergic diseases, such as asthma, allergic rhinitis and atopic dermatitis.
The immediate type-I allergic reaction, such as bronchoconstriction in asthma, sneezing in allergic rhinitis and itching in atopic dermatitis, are initiated by the interaction of antigens, such as pollen or house dust, with their specific IgE captured on mast cells and basophils. More specifically, high affinity IgE receptor (FceRI) on the surface of mast cells and basophils traps IgE, which then recognizes antigen. Antigen-IgE interaction engages FceRI, resulting in elicitation of cellular response such as, histamine and PGD2 release to cause the immediate allergic reaction. Activated cells also produce leukotrienes and cytokines to cause the late inflammatory response, such as tissue eosinophilia.
Syk tyrosine kinase (Taniguchi, T. et. al., J. Biol. Chem. 266: 15790-15796 (1991)) is one of tyrosine kinases involved in these cellular responses. Costello, P. S. et. al. suggests that Syk tyrosine kinase is indispensable for the 3 cellular responses; degranulation, lipid mediator synthesis and cytokine production with the use of mast cells derived from syk knockout mice (Oncogene 13: 2595-2605 (1996)). Stenton, G. R. et. al. discloses that the Syk antisense oligo DNA inhalation suppress the parasite antigen-induced pulmonary inflammation in rats (J. Immunol., 164: 3790-3797 (2000)). Therefore, Syk tyrosine kinase inhibitors are expected to suppress both immediate allergic reaction and late inflammatory response.
Further, various genetic and pharmacological studies suggest Syk tyrosine kinase plays important roles in other type of cells. Syk is reported to be essential for the FcγRs-mediated phagocytosis in monocytes/macrophages (Matsuda, M. et. al., Mol. Biol. Cell 7: 1095-1106 (1996)), pre BCR-mediated B cell maturation (Cornall, R. J. et. al., Proc. Natl. Acad. Sci. USA 97: 1713-1718 (2000)), GM-CSF/IL-5-induced eosinophil survival (Yousefi, S. et. al., J. Exp. Med., 183: 1407-1414 (1996)), collagen-induced platelet activation (Poole, A. et. al., EMBO J. 16: 2333-2341 (1997)), differentiation of fibroblast to adipocytes (Wang, H. and Malbon, C. C., J. Biol. Chem. 274: 32159-32166 (1999)) and β-amyloid peptide-/prion peptide-induced neurotoxic product generation in microglia (Combs, C. K. et. al., J. Neurosci. 19: 928-939 (1999)).
Therefore, Syk tyrosine kinase inhibitors have possibilities to prevent antibody dependent cellular cytotoxicity (ADCC), antibody related diseases, eosinophilic inflammation, platelet agglutination, obesity and Alzheimer/prion disease, respectively.
As an effective agent for a Syk inhibitor, pyrimidine-5-carboxyamide derivatives represented by general formula 
wherein Xd represents O, S, NR1d, CO, NR1dCO, CONR1d, C═N—OR1d or a bond; Yd represents lower alkylene optionally substituted by OR1d or NHR1d or a bond; Zd represents O, NR2d or attachment; Ad represents H, optionally substituted lower alkyl, lower alkyl optionally substituted by CO, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl or optionally substituted saturated heterocycle including N; B represents optionally substituted aryl or optionally substituted heteroaryl; R1d and R2d represent H, lower alkyl, or —CO-lower alkyl, are disclosed in WO99/310773.
As an effective agent for a variety of diseases, various imidazopyrimidine derivatives and triazolopyrimidine derivatives have been studied. For example, Abignente Enrico et al., (Farmaco (1991), 46(10), 1099-110) discloses the compound of the following formula: 
(wherein R1p represents CO2H, CO2Et, CONH2, CH2CO2H; R2p represents Me, OMe; and R3p represents OMe, Me, Cl) having anti-inflammatory activity.
Danagulyan, G. G. et al., (Khim. Geterotsikl. Soedin. (1992), (2), 225-7) discloses the compounds of the following formula: 
U.S. Pat. No. 4,639,445 discloses the compounds of the following formula 
wherein Re is OH and n is 1 or 2, useful as bronchodilators.
U.S. Pat. No. 4,591,588 discloses the compounds of the following formula 
wherein n is 1 or 2, which shows bronchodilator activity.
However, none of the reference relating to imidazopyrimidine derivatives and triazolopyrimidine derivatives has aromatic group at C-7 position nor suggest Syk tyrosine kinase inhibitory activity.